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Biomedical subjects

D Taylor

Publications and source records attributed to D Taylor.

At least 127 records · Page 7Linked to original sources

Vertical or asymmetric nystagmus need not imply neurological disease.

AIM: To indicate that congenital idiopathic nystagmus (CIN) and sensory defect nystagmus (SDN) can be vertical or asymmetric in some children. METHODS: Of 276 children presenting with nystagmus for electrophysiological testing, 14 were identified as having CIN or SDN, yet had a nystagmus which was either vertical (n=11) or horizontal asymmetric (n=3). Flash electroretinograms and flash and pattern visual evoked potentials (VEPs) were recorded in all patients. Eye movement assessment, including horizontal optokinetic nystagmus (OKN) testing, was carried out in 11/14 patients. RESULTS: Eight patients (seven with vertical, one with asymmetric horizontal nystagmus) had congenital cone dysfunction. One patient with vertical and another with asymmetric nystagmus had cone-rod dystrophy. One patient with vertical upbeat had congenital stationary night blindness. Two patients (one downbeat, one upbeat nystagmus) had normal electrophysiological, clinical, and brain magnetic resonance imaging findings and were classified as having CIN. One patient with asymmetric nystagmus showed electrophysiological and clinical findings associated with albinism. Horizontal OKN was present in 80% of patients tested, including the three cases with horizontal asymmetric nystagmus. This is atypical in both CIN and SDN, where the OKN is usually absent. CONCLUSIONS: Vertical and asymmetric nystagmus are most commonly associated with serious intracranial pathology and its presence is an indication for neuroimaging studies. However, such nystagmus can occur in children with retinal disease, albinism, and in cases with CIN. These findings stress the importance of non-invasive VEP/ERG testing in all cases of typical and also atypical nystagmus.

Child, Preschool↗

Reconstruction of the lateral ligaments of the ankle using semi-tendinosis graft.

Injury to the lateral ligaments of the ankle is one of the most common sports-related injuries. Although these injures generally resolve with non-operative treatment reconstruction of the lateral ligaments of the ankle is occasionally necessary. We report the surgical technique and result of reconstruction of the anterior talo-fibular ligament using a semi-tendinosis free graft in 26 patients with an average follow-up of 24 months. 81% of patients reported complete resolution or substantial improvement in instability, swelling and sharp pain. Episodes of functional instability persisted in five patients post operatively. No significant differences were noted between the operated and contra-lateral non-operated ankle in range of motion or uniaxial balance assessment. Kin-Com testing of hamstring strength showed no differences between sides. Short term results suggest that this ligament reconstruction provides good results without sacrifice of peroneal function and has minimal donor site morbidity.

Adolescent↗

Selective serotonin reuptake inhibitors: a review of efficacy and tolerability in depression.

Selective serotonin reuptake inhibitors (SSRIs) are now generally regarded as effective and better tolerated alternatives to tricyclic antidepressants (TCAs) for the treatment of depression. SSRIs also seem to be as well tolerated as moclobemide, mirtazapine, venlafaxine, reboxetine and nefazodone and show comparable efficacy. Minor differences have been observed between some SSRIs and some of the newer antidepressants but these findings are far from conclusive. Widespread use of the SSRIs has highlighted some unforseen adverse effects associated with SSRIs, namely hyponatraemia, EPSE and sexual dysfunction. Overall, differences in efficacy and tolerability between individual SSRIs are small and clinically insignificant.

Clinical Trials as Topic↗

Tolerability of atypical antipsychotics.

Atypical antipsychotics are expected to be better tolerated than older antipsychotics because of their lower propensity to cause certain adverse effects. All atypical drugs have been shown to cause fewer acute extrapyramidal symptoms (EPS) than a standard typical agent (usually haloperidol) and some (clozapine, sertindole and quetiapine) appear to cause these effects no more often than placebo. In the longer term, clozapine, olanzapine and (less robustly) other atypical antipsychotics are thought to cause less tardive dyskinesia than typical antipsychotics. Problems caused by hyperprolactinaemia occur less often with some atypical antipsychotics than with typical drugs although risperidone and amisulpride appear to have no advantages in this respect. Other adverse effects may occur as frequently with some atypical antipsychotics as with some typical drugs. Clozapine, risperidone and quetiapine are known to cause postural hypotension; clozapine, olanzapine and quetiapine are clearly sedative; and anticholinergic effects are commonly seen with clozapine, and, much less frequently, with olanzapine. Some adverse effects are more frequent with atypical drugs. Idiosyncratic effects seem particularly troublesome with clozapine and, to a lesser extent, sertindole, olanzapine and zotepine. Bodyweight gain is probably more problematic with atypical antipsychotics than with typical drugs. Overall tolerability, as judged by withdrawals from therapy, is not clearly proven to be better with atypical drugs, although some individual trials do indicate an advantage with atypical agents. Differences in tolerability between individual atypical antipsychotics have not been clearly shown. The tolerability profile of atypical drugs certainly benefits from a lower incidence of acute EPS effects, along with less certain or less uniform benefits in symptomatic hyperprolactinaemia or tardive dyskinesia. Other, perhaps more trivial, adverse effects militate against their good tolerability, and effects such as bodyweight gain may severely reduce tolerability. Without clear advantages in tolerability in patient groups used in trials, drug choice in regard to adverse effects should continue to be on a patient to patient basis.

Antipsychotic Agents↗

Increased interleukin-10 and macrophage inflammatory protein-1 alpha release from blood monocytes ex vivo during late-phase response to allergen in asthma.

BACKGROUND: We determined the effect of late-phase responses to allergen challenge of mildly allergic asthmatic patients on the expression and release of the cytokines IL-10 and MIP-1alpha from peripheral blood monocytes. METHODS: Sixteen mildly allergic asthmatics were exposed to increasing concentrations of allergen aerosol. Nine demonstrated an early response alone (single responders), while seven had an early followed by a late response (dual responders). Monocytes were isolated from venous blood before and 24 h after allergen challenge, and placed in short-term culture for determination of IL-10 mRNA expression by reverse-transcription polymerase chain reaction and protein release. MIP-1alpha protein release was measured by radioimmunoassay. RESULTS: IL-10 mRNA expression was significantly higher in dual responders than early responders alone, for unstimulated monocytes or for monocytes exposed to lipopolysaccharide or IL-1beta. In addition, the release of IL-10 and MIP-1alpha from monocytes of dual responders was also enhanced. CONCLUSIONS: Circulating monocytes are primed to release more of the cytokines, IL-10 and MIP-1alpha, in dual but not in single responders, at 24 h after allergen. They may contribute to allergen-induced inflammatory responses in the airways.

Adult↗

Phenotypic variability and asymmetry of Rieger syndrome associated with PITX2 mutations.

PURPOSE: Rieger syndrome is an autosomal dominant condition characterized by a variable combination of anterior segment dysgenesis, dental anomalies, and umbilical hernia. To date, reports have shown mutations within the PITX2 gene associated with Rieger syndrome, iridogoniodysgenesis, and iris hypoplasia. The purposes of this study were to determine the range of expression and intrafamilial variability of PITX2 mutations in patients with anterior segment dysgenesis. METHODS: Seventy-six patients with different forms of anterior segment dysgenesis were classified clinically. DNA was obtained and screened by means of polymerase chain reaction (PCR)-single-stranded conformation polymorphism (SSCP) and heteroduplex analysis followed by direct sequencing. RESULTS: Eight of 76 patients had mutations within the PITX2 gene. Anterior segment phenotypes show wide variability and include a phenocopy of aniridia and Peters', Rieger, and Axenfeld anomalies. Mutations include premature terminations and splice-site and homeobox mutations, confirming that haploinsufficiency the likely pathogenic mechanism in the majority of cases. CONCLUSIONS: There is significant phenotypic variability in patients with PITX2 mutations, both within and between families. Developmental glaucoma is common. The umbilical and dental abnormalities are highly penetrant, define those at risk of carrying mutations in this gene, and guide mutation analysis. In addition, there is a range of other extraocular manifestations.

Anterior Eye Segment↗

Signal transduction mechanisms mediating secretion in goldfish gonadotropes and somatotropes.

The intracellular signal transduction mechanisms mediating maturational gonadotropin and somatotropin secretion in goldfish are reviewed. Several major signaling mechanisms, including changes in intracellular [Ca2+], arachidonic acid cascades, protein kinase C, cyclic AMP/protein kinase A, calmodulin, nitric oxide, and Na+/H+ antiport, are functional in both cell types. However, their relative importance in mediating basal secretion and neuroendocrine-factor-regulated hormone release differs according to cell type. Similarly, agonist- and cell-type-specificity are also present in the transduction pathways leading to neuroendocrine factor-modulated maturational gonadotropin and somatotropin release. Specificity is present not only in the actions of different regulators within the same cell type and with the same ligand in the two cell types, but this also exists between isoforms of the same neuroendocrine factor within a single cell type. Other evidence suggests that function-selectivity of signaling may also result from differential modulation of Ca2+ fluxes from different sources. The interaction of different second messenger systems provide the basis by which regulation of maturational gonadotropin and somatotropin release by multiple neuroendocrine factors can be integrated at the target cell level.

Animals↗

More than personal change: effective elements of symptom management.

Symptoms are the most common reason people seek health care. Although the menstrual cycle, a normative process, is not a chronic illness, about 10% to 15% of women experience severe recurring symptoms associated with the menstrual cycle that can be considered a chronic illness. Severe perimenstrual symptoms, although distressing for some women, provide a model for understanding complex gender-specific conditions that include biological, psychosocial, and cultural factors, and have application to other women's health problems such as stress-related conditions (heart disease, arthritis, immune system disorders), psychiatric disorders, or normative menstrual cycle transitions (menarche, postpartum, menopause). The Perimenstrual Symptom Management Program, developed by the author, was evaluated to determine the short-term and long-term effectiveness of a multimodal, nonpharmacological treatment package aimed at relieving the symptom and stress experience as well as increasing health behaviors. Selected results from this longitudinal clinical trial will be presented along with examples of effective elements of personal and environmental strategies for symptom management and health promotion. Recommendations for clinical application of these research findings will be presented with a focus on both patient outcomes and intervention processes for personal and environmental therapeutic change.

Adult↗

Visualization of head-head interactions in the inhibited state of smooth muscle myosin.

The structural basis for the phosphoryla- tion-dependent regulation of smooth muscle myosin ATPase activity was investigated by forming two- dimensional (2-D) crystalline arrays of expressed unphosphorylated and thiophosphorylated smooth muscle heavy meromyosin (HMM) on positively charged lipid monolayers. A comparison of averaged 2-D projections of both forms at 2.3-nm resolution reveals distinct structural differences. In the active, thiophosphorylated form, the two heads of HMM interact intermolecularly with adjacent molecules. In the unphosphorylated or inhibited state, intramolecular interactions position the actin-binding interface of one head onto the converter domain of the second head, thus providing a mechanism whereby the activity of both heads could be inhibited.

Animals↗

Human phase I vaccine trials of 3 recombinant asexual stage malaria antigens with Montanide ISA720 adjuvant.

Two phase I vaccine trials were conducted to test the immunogenicity and safety of a vaccine containing three recombinant malaria antigens from the asexual stage of Plasmodium falciparum. The three antigens are a fragment of MSP1 (190LCS.T3); MSP2 and a portion of RESA and were formulated in Montanide ISA720 adjuvant. These trials investigated the dose response of each antigen for eliciting both antibody and T-cell responses and the immunogenicity of a mixture of the antigens compared with the antigens injected separately. All three antigens elicited both antibody and T-cell responses. Strong T-cell responses were observed with 190LCS.T3 and RESA with stimulation indices exceeding 100 for peripheral blood leucocytes in some individuals. The antibody responses were generally weak. The human antibody responses observed with MSP2 in Montanide ISA720 were not significantly different from those obtained in an earlier trial which used MSP2 with alum as the adjuvant. No antigenic competition was observed: volunteers receiving a mixture of antigens had similar responses to those receiving the three antigens at separate sites. Tenderness and pain at the injection site were common over the first few days following immunization. In some volunteers, especially those receiving the highest doses tested, there was a delayed reaction at the injection site with pain and swelling occurring approximately 10 days after injection.

Adjuvants, Immunologic↗

Effectiveness of professional--peer group treatment: symptom management for women with PMS.

The purpose of this intervention study was to determine short- and long-term effectiveness of a symptom management intervention aimed at relieving the distress associated with premenstrual syndrome (PMS). The PMS Symptom Management Program (PMS-SMP), a package of nonpharmacological strategies involving self-monitoring, personal choice, self-regulation, and self/environmental modification, was administered within a group combining peer support and professional guidance to 91 women classified with severe PMS (early treatment groups n = 40; waiting treatment groups n = 51). Repeated behavioral measures (symptom severity and personal resources/demands) were obtained on five occasions: two menstrual cycles prior to treatment and at 3, 6, 12, and 18 months after treatment. A package of symptom management strategies was effective in reducing PMS severity by 75%, premenstrual depression, and general distress by 30-54%, as well as increasing well-being and self-esteem in women experiencing severe PMS. These results compare favorably with antidepressant drug treatment studies that report a 40-52% reduction in PMS severity. The most marked improvement was found in the first 3 months after treatment; however, improvement was maintained or enhanced in the long-term follow-up. Although focused on perimenstrual symptom relief, these strategies are generally health promoting and can be applied to other women's health conditions.

Adaptation, Psychological↗

Factors affecting continuation rates of DMPA.

A prospective study was conducted with 430 new depot medroxyprogesterone acetate (DMPA) acceptors to estimate continuation rates and investigate factors associated with length of use. Data were collected on services received and sociodemographic characteristics of participants. Women were enrolled over the course of 1 year and were followed for up to 13 months. Failure to return to the same clinic within 104 days of the last injection was the outcome of interest. The 3-, 6-, 9-, and 12-month continuation rates were 68%, 67%, 55%, and 51%, respectively. In the bivariate analysis, women who were told to return to the clinic for side effects were more likely to continue using DMPA than those who were not given such advice (p <0.05). Likewise, women who received information on DMPA efficacy, side effects, and amenorrhea were more likely to continue using DMPA compared to those who did not receive such information (p <0.05). A proportional hazards regression model was constructed to estimate the simultaneous effect of various factors on length of use. In results consistent with the bivariate analysis, women who were told to return to the clinic were 2.7 times more likely to continue using DMPA compared to women who did not receive that advice. Likewise, women who were told about the possibility of amenorrhea were 2.5 times more likely to continue using DMPA compared to those who did not receive that information. The regression model also identified new factors such as number of children, attitude toward menstruation, lactating at admission, and spousal input on method choice. The findings suggest that providers play an important role in ensuring the highest possible continuation rates for DMPA.

Adolescent↗

Compression data on bovine bone confirms that a "stressed volume" principle explains the variability of fatigue strength results.

The literature contains many measurements of the fatigue properties of compact bone, but these experimental results have been difficult to interpret and use due to a large amount of apparent scatter: variation in the number of cycles to failure for a given cyclic stress or strain range. Recently Taylor (1998a, Journal of Orthopaedic Research, 16, 163-169) showed that much of this scatter could be explained using a statistical model which took into account specimen size, or more specifically stressed volume. The present paper describes an attempt to test this model by using it to predict some new data, for bovine bone tested in compressive loading at room temperature at physiological loading rates. Twenty specimens were tested at the same applied load range (100 MPa). The theory was able to predict the mean behaviour of the specimens very well, with an accuracy (expressed in terms of stress) of 2%. It was also able to predict the degree of scatter (i.e. the variation of Nf), which was shown to be similar to that measured by other workers.

Animals↗

Novel self-sampling culture method to monitor excretion of live, oral Shigella flexneri 2a vaccine SC602 during a community-based phase 1 trial.

A culture technique for assessing the excretion of live enteric vaccines was developed and verified during an outpatient safety trial of the Shigella flexneri 2a SC602 vaccine. Preliminary studies showed that SC602 could be recovered on Hektoen enteric (HE) agar plates that had been inoculated with seeded stools in one quadrant, held for up to 48 hours, streaked for isolation, and incubated for 24 +/- 6 hours. Recovery results on HE plates held at 4 degrees C and 25 degrees C were comparable; however, 4 degrees C better inhibited overgrowth before streaking. To prepare for a community-based vaccine trial, volunteers were trained to self-sample fresh stool and to swab-inoculate a single quadrant of HE agar. The trial began with 36 volunteers ingesting 2.5 x 10(4) CFU of SC602 in bicarbonate buffer. During the study, volunteers inoculated HE plates with fresh stool, stored the plates at 4 degrees C, and delivered them to the laboratory within 48 hours. A microbiologist then streaked the HE for isolation, incubated the plates at 35 degrees C +/- 2 degrees C for 24 +/- 6 hours, and identified presumptive S. flexneri colonies by slide agglutination with poly-group B antiserum. The attenuating genetic signature of SC602 was confirmed on selected isolates with the polymerase chain reaction with two specific DNA primer sets. Vaccine was detected from 20% of volunteers on day 1, increasing to 86% by day 4, and all but one vaccinee had excreted SC602 at least once by day 7. The latest initial SC602 detection occurred on day 7, the longest excretion occurred in one vaccinee on day 33, and excretion throughout the trial was intermittent. The trial was terminated by ciprofloxacin treatment on day 35. Volunteer compliance with self-sampling and HE plating was excellent because of the convenience of the method, and the advantage of immediate "bedside" plating was evident in the high recovery rate of excreted vaccine. This method can be applied in other trials of live enteric vaccines that require accurate sampling of excreted organisms.

Administration, Oral↗

Immunohistochemical detection of p53 protein accumulation in head and neck cancer: correlation with p53 gene alterations.

The genetic and functional status of the p53 gene may be an important factor in guiding therapeutic strategies for patients with cancer. The purpose of this study was to determine whether p53 immunohistochemistry (IHC) accurately reflects the mutational status of the p53 gene and to determine whether p53 IHC independently predicts tumor responsiveness to radiation therapy for patients with HNSCC. p53 IHC was performed using the monoclonal antibody DO7 on tumors from 85 patients with HNSCC treated with primary or adjuvant radiation. The p53 status in all of these tumors was previously assessed by direct sequence analysis of exons 5 through 9: 49 tumors were p53 wild-type, and 36 harbored p53 gene mutations. All patients were well characterized with respect to locoregional recurrence, distant spread, and survival. Positive p53 staining was observed in 53 of the 85 cases (62%). Only 27 (51%) of these 53 IHC-positive cases harbored gene mutations in exons 5 through 9; 23 (72%) of the 32 IHC-negative cases did not harbor mutations. The overall correlation rate between IHC and sequencing was 59% (P < .04, chi2). Discordant results were observed for 35 (41%) cases, including 26 IHC-positive cases and 9 IHC-negative cases. In 7 of 9 cases, false-negative staining was due to a nonsense or splice-site mutation. p53 IHC was not predictive of overall survival (P = .37) or disease-free survival (P = .95). In a sizable number of cases, p53 IHC does not reflect the mutational status of the p53 gene. Specific types of alterations (eg, truncating mutations) and other factors may contribute to this poor correlation. Moreover, p53 IHC does not appear to be an independent predictor of tumor responsiveness to radiation in patients with HNSCC.

Carcinoma, Squamous Cell↗